Targeted proteasomal degradation of m6A-reader proteins in colorectal carcinoma (B08)

• Subject Area: Cell Biology ; Hematology, Oncology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514894665

In Project B08 we will elucidate MYC-dependent mechanisms in colon carcinoma (CRC). Mechanistically, we will study if the m6A reader YTHDC1 underpins the ability of ubiquitylated MYC multimers to repair DNA damage and use cutting-edge degradation systems to investigate how loss of YTHDF1 and YTHDC1 impacts CRC viability. We will explore the requirements for targeted proteasomal degradation of m6A reader proteins by a novel oligonucleotide-based platform termed RNA-PROTACs in terms of oligomer design and positioning of an E3 ligase ligand, and we will investigate if the m6A reader YTHDC1 can be targeted for proteasomal degradation by a small-molecule PROTAC.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 387: Functionalizing the Ubiquitin System against Cancer - UbiQancer
• Applicant Institution: Technische Universität München (TUM)
• Project Heads: Professor Dr. Andreas Brunschweiger; Dr. Dimitrios Papadopoulos